A linear quantitative structure–activity relationship (QSAR) study that encodes various aspects of physicochemical,topological and electronic descriptors has been developed for a series of 1,3,4-thiadiazole-2-thione derivatives (1a-r and 2a-c). The carbonic anhydrase IX inhibitory activity of the candidates under study (1a-r and 2a-c) were correlated to the selected parameters using stepwise linear regression analyses to achieve the best QSAR model. Promising results were obtained with the employed tetra-parametric model indicating that the information approach used in the present investigation is quite useful for modeling carbonic anhydrase IX inhibitors.